In many vertebrates, an increase in plasma gonadal steroids is detectable soon after the start of courtship or sexual behavior. In the course of studies aimed at understanding how environmental and behavioral stimuli produced changes in the brain that result, in turn, in altered endocrine secretions, we noted the appearance of GnRH-positive mast cells in the medial habenula. The mast cells were present in animals which were sacrificed 2 hours after the start of courtship, were few in animals housed in isolation, and were virtually absent in castrates. Brain mast cells are a widespread phenomenon. Their occurrence was documented in a variety of species when methods to detect biogenic amines first became widely available in the 1970's. While peripheral mast cells have been widely studied, especially in relation to allergy, the possible function of brain mast cells has been little explored. The first aim of this proposal is to delineate the context(s) (e.g. stress, response to novelty, sexual behavior) in which changes occur in number and state of activation of brain mast cells in the medial habenula. Our studies will be specific changes in mast cell number. The habenula is a conservative structure known to serve as link between forebrain and midbrain structures. The second broad goal of the research is to understand the normal physiological function of mast cells in the medial habenula. To this end, we will delineate behavioral function(s) of the medial habenula, and of its efferents and afferents. The overall hypothesis to be tested is that brain mast cells represent a novel signaling system, operating at the interface of the neural, endocrine and the immune systems.